Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide after docetaxel failure: the international retrospective observational STABEN study

Abstract

BackgroundStatins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption of essential steroidogenic processes. We investigated the effects of statin use on clinical outcomes in patients with mCRPC receiving abiraterone or enzalutamide.Materials and methodsThis was a retrospective multicenter study including patients that received abiraterone or enzalutamide for mCRPC. The effect of concurrent statin use on outcomes was evaluated. The associations of statins with early (≤12 weeks) prostate-specific antigen (PSA) declines (> 30%), cancer-specific survival and overall survival (OS) were evaluated after controlling for known prognostic factors.ResultsFive hundred and ninety-eight patients treated with second-line abiraterone or enzalutamide after docetaxel for mCRPC were included. A total of 199 men (33.3%) received statins during abiraterone/enzalutamide treatment. Median OS was 20.8 months (95% CI = 18.3–23.2) for patients who received statins, versus 12.9 months (95% CI = 11.4–14.6) for patients who did not receive statins (P < 0.001). After adjusting for age, alkaline phosphatase, PSA, neutrophil-to-lymphocytes ratio, Charlson comorbidity score, Gleason score, visceral disease, hemoglobin, opiate use and abiraterone versus enzalutamide treatment, the use of statin therapy was associated with a 53% reduction in the overall risk of death (hazard ratio [HR] = 0.47; 95% CI = 0.35–0.63; P < 0.001). Statin use was also associated with a 63% increased odds of a > 30% PSA decline within the first 12 weeks of treatment (OR = 1.63; 95% CI = 1.03–2.60; P = 0.039).ConclusionsIn this retrospective cohort, statin use was significantly associated with both prolonged OS and cancer-specific survival and increased early > 30% PSA declines. Prospective validation is warranted.

The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta‐analysis

“…A total of 66 articles were excluded after the review of abstracts, and 35 studies were potentially eligible and evaluated in detail. Overall, nine studies with 101 773 patients were identified that were eligible for inclusion in the meta‐analysis . Specifically, three studies were related to abiraterone or enzalutamide, whereas the rest six articles were about ADT .…”

“…However, another meta‐analysis demonstrated that such a potentially beneficial effect of statins on PCa was only found in the patients receiving radiotherapy, but not in those who accepted radical prostatectomy . Intuitively, whether the effect of statins on PCa could vary along with treatment modality arouses increasing attention in clinical practice …”

“…Newer agents, including abiraterone and enzalutamide, have been approved to manage patients with metastatic castration‐resistant prostate cancer (mCRPC) . Although a handful of studies about the influence of statins on treatment outcomes in PCa patients who were treated with ADT or abiraterone/enzalutamide have been published, results are inconsistent and vary by studies. Considering that the combination of statins and ADT for PCa could possibly generate additional impacts on the overall treatment outcomes, investigations focusing on the most appropriate target patient population are of great clinical importance to optimize treatment responses and improve the quality of life in PCa patients.…”

Association of Body Composition With Survival and Treatment Efficacy in Castration-Resistant Prostate Cancer

“…ARSi drives changes in metabolic profiles and body composition. Previous studies demonstrate relationships between ARSi therapy and lipid metabolism and statin use (23)(24)(25). Both abiraterone and enzalutamide can induce increases in body fat mass and decreases in lean body mass (26,27).…”

Para-Toluenesulfonamide Induces Anti-tumor Activity Through Akt-Dependent and -Independent mTOR/p70S6K Pathway: Roles of Lipid Raft and Cholesterol Contents

“…It is noteworthy that the use of statins, HMG-CoA reductase inhibitors on lowering lipid, has been reported to be clinically associated with prolonged overall survival and cancer-specific survival in patients with metastatic CRPC receiving abiraterone or enzalutamide although future validation is warranted ( Gordon et al, 2018 ). The research supports the potential of the combination treatment of CRPC patients with PTS and therapeutic drugs.…”